What is an “ongoing” clinical trial? An analysis of different sources revealed heterogeneous definitions of when a clinical trial starts and ends: a meta-research study

ABSTRACT BACKGROUND: Although the concept of an “ongoing study” seems self-explanatory, it is difficult to determine whether a trial is underway. OBJECTIVE: To analyze the definitions of “ongoing clinical trial” across different clinical trial registries, methodological guidelines, and other sources. DESIGN AND SETTING: This meta-research study was conducted at the Universidade Federal de São Paulo (UNIFESP), Brazil. METHODS: We performed a cross-sectional analysis of relevant clinical trial registry databases, methodological guidelines for conducting systematic reviews, and other sources that would define or regulate clinical trials. RESULTS: We identified various heterogeneous definitions used by eligible sources at both the start and end of a clinical trial. The starting criteria used were as follows: when the team is planning the protocol, when permission is given to conduct the study, or when the first participant is enrolled. Some sources used the time at which the last outcome data was collected as a criterion to determine the end of the trial. The International Committee of Medical Journal Editors stated that a study is still “ongoing” during the analysis process. Several sources use a vague definition or present no clear criteria for defining the start or end of a study. CONCLUSION: The concept of “ongoing clinical trials” lacks a transparent and homogeneous definition across relevant sources. A consensus on this concept is important to facilitate the evaluation of available evidence and conduct research synthesis. Further efforts are necessary to determine the best definition for the start and end of a clinical trial.


INTRODUCTION
The selection and classification of primary studies is an elementary and key component when assessing medical literature or conducting a systematic review. [1][2][3][4] However, these processes can be highly subjective and lead to different decisions or judgments. 5 A common approach, mainly in interventions/effectiveness reviews, is to classify any study that has not been completed as "ongoing clinical trial. " 4 The problem with this approach is that the definition of when a study starts or ends may not be uniform and impose challenges when assigning a trial as "ongoing. " 4 Although the concept of an ongoing study appears self-explanatory, it is difficult to determine whether a trial is underway.
For instance, one may state that a clinical trial begins when the first patient is enrolled or has received the first intervention dose or even when the first outcome data is collected. The start of a study can also be defined as the time when the primary objective is conceived or when the team is assembled. A study's end may also have different definitions, such as when the last participant was enrolled, when the last outcome data were collected, or when all analyses were completed.
Considering the challenges in uniformly categorizing ongoing studies, we aimed to map the definition criteria adopted by major sources.

OBJECTIVE
This study aimed to analyze the definitions of an "ongoing clinical trial" across different clinical trial registries and methodological guidelines.  We also extracted their definitions to detect any mention regarding "ongoing clinical trials. " The sources were chosen based on our expertise, and we attempted to cover information from any relevant clinical trial registry database, methodological guidelines to conduct systematic reviews, and other sources that would define or regulate clinical trials.
The search and data extraction date was January 16, 2022.
Data extraction was aided using an Excel sheet and the results were presented narratively.

RESULTS
After analyzing eligible sources, we found various definitions for both the start and end of a clinical trial ( Table 1).
The ISRCTN registry considers a study to start when the team is planning the protocol, 7 and the European Union Clinical Trials register defines the study start date as when permission is given to conduct the study. 8 The National Institutes of Health (Clinicaltrials. gov/) registry defines study initiation as when the first participant is enrolled. 6 Some sources used the time at which the last outcome data was collected as a criterion to determine the end of the trial.
The International Committee of Medical Journal Editors states that

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a study is still "ongoing" during the analysis process, 12 which means that the study ends only after the end of the data collection process. In light of these definitions of "ongoing studies, " the process of categorizing studies may vary substantially among reviewers, thereby affecting reproducibility and transparency of the reviews.
The category of ongoing clinical trials is not the only one that lacks consensus regarding its definition. In a previous study, 5 we analyzed the justifications for considering a study to be "awaiting  classification" in a sample of published systematic reviews, and we found a high proportion of conflicting or unclear justifications.
Our results showed that study categorization still lacks clear definitions and recommendations and that strict criteria need to be applied to increase transparency and improve the reproducibility of systematic reviews. A homogeneous and clear definition of ongoing studies must be adopted through trial registration databases and systematic review development guidelines.
Our analysis has limitations because we adopted an unstructured search for relevant sources. However, although anecdotal, our results showed that major sources have heterogeneous definitions for the start and end of a clinical trial, and it is reasonable to assume that this is a widespread problem in the medical literature.

CONCLUSION
The concept of "ongoing" clinical trial lacks transparent and homogeneous definitions across relevant sources. A consensus on this concept is important to facilitate the evaluation of available evidence and conduct research synthesis and systematic reviews. Further efforts are necessary to determine the best definition for the start and end of a clinical trial.